Ovarian cancer results in more deaths than any other cancer of the female reproductive system. However, improvements in surgical techniques and chemotherapy have led to an increase in the 5-year survival rate from 37 percent in 1976 to 45 percent in 2006. Because of advances in therapeutic modalities, the number of ovarian cancer survivors for whom primary goals are to maximize disease-free survival and maintain quality of life (QOL) is growing. As such, survivorship issues are becoming increasingly important. Various studies report poor QOL in ovarian cancer patients. Research is needed to develop and test interventions to improve QOL in ovarian cancer survivors. Currently, the American Cancer Society recommends a physically active lifestyle for cancer survivors to increase disease-free survival from cancer and other chronic diseases, and to improve quality of life. Studies of a strong benefit of physical activity on improving QOL following other types of cancer treatment, e.g., breast cancer, are well documented in the literature;yet very few studies of physical activity and QOL after a diagnosis of ovarian cancer have been published. There are also no published data examining whether physical activity may improve ovarian cancer survival or surrogate markers of survival. Although the impact of exercise on ovarian cancer survival is unknown, it may play a role via weight control, since obesity has been shown in some studies, but not all, to be negatively associated with survival. Results from observational studies also suggest an inverse association between physical activity and risk of ovarian cancer. Possible biological explanations for the associations between obesity and low levels of physical inactivity and ovarian cancer risk and mortality involve the potential role of estrogens, insulin, insulin-like growth factors (IGFs) C-reactive protein (CRP), leptin, CA-125, prolactin, osteopontin, and macrophage inhibitory factor. Given the promising results from our randomized trials of exercise interventions in healthy women and breast cancer survivors, and our QOL interventions in ovarian cancer survivors, a trial examining the impact of exercise in improving QOL and surrogate markers of prognosis in ovarian cancer survivors is warranted. We propose to evaluate, in 230 sedentary women diagnosed with Stage I-III ovarian cancer, the impact of a 6-month, moderate-intensity, aerobic exercise intervention vs. attention control upon QOL and surrogate markers of prognosis. Women will be randomized to an exercise program or attention control group. Women randomized to exercise will participate in 150 minutes of aerobic exercise per week (e.g., five 30-min sessions/wk). We will conduct baseline and 6-month clinic visits to evaluate the effect of exercise on QOL and surrogate markers. Our study, the largest exercise trial in cancer survivors, could be a "proof of principal" and will provide critical information in understanding the potential mechanisms through which physical activity may impact ovarian cancer risk and prognosis. PUBLIC HEALTH RELEVANCE: Despite an increase in longevity, surviving ovarian cancer often brings an array of unpleasant side effects and compromises in QOL. Our proposed trial will be the first study to test whether exercise compared with attention control has a beneficial impact on quality of life, fitness and surrogate markers of prognosis. Our study will examine the effect of exercise on QOL and surrogate markers of ovarian cancer prognosis in 230 ovarian cancer survivors. Our study, the largest exercise trial in ovarian cancer survivors, could be a "proof of principal" and will also help shape post-treatment physical activity guidelines for millions of cancer survivors.